[Nitrates and coronary vascular endothelium dysfunction].
Since the classical studies by Furchgott and Zawadski (Nature, 1980, 286, 373-376), the vascular endothelium is known to play a fundamental role in the regulation of haemostasis and vasomotor activity. This is primarily due to its strategic interface position between the circulating blood and smooth muscle cells of the media. Due to the presence of specific receptors to mediators released during platelet aggregation (thrombin, ATP, serotonin, PAF, etc.), and the presence of mechanoreceptors sensitive to shearing forces generated by blood flow along the vessel wall, the endothelium is able to release, at the two poles of the cell, vasodilator and antiaggregant substances called "endothelium derived relaxing factors" (EDRFs), the best known for which are nitric oxide (NO) ans prostacyclin (PGl2). In the absence of endothelium (angioplasty), or in the case of endothelium dysfunction related to cardiovascular diseases such as hypertension, heart failure, atherosclerosis or diabetes, EDRF synthesis is absent or defective and its oxidative catabolism in increased (particularity by superoxide anion), resulting in varying degrees of disorders of haemostasis (thrombosis) and/or arterial and venous vasomotor activity. The only known effective treatment to palliate these dysfunctions is exogenous NO, supplied in the form of nitrate (nitroglycerin, isosorbide dinitrate, 5-mononitrate) or "NO donors" (Sin1, nitroprussate). The advantage of these substances is that their vasodilator effects (and, in some cases, their antiaggregant effects) are strictly endothelium-independent and they remain effective regardless of the causes and severity of endothelial dysfunction.
Berdeaux
A
A
Département de Pharmacologie, Faculté de Médecine Paris Sud, le Kremlin Bicêtre, France.
Dubois-Randé
J L
JL
Hittinger
L
L
D003331:Coronary Vessels / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology*; D006801:Humans; D009566:Nitrates / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D009566:Nitrates; D014665:Vasodilator Agents
Dérivés nitrés et dysfonctionnement de l'endothélium vasculaire coronaire.